DESCRIPTION (Applicant?s abstract): The research proposed involves studying in humans in vivo the effect of acute resistance exercise and mixed amino acid supplementation on skeletal muscle protein synthesis and the regulation of intracellular signal transduction. In Specific Aim 1, healthy adults will be studied. Protein synthesis will be assessed by muscle protein enrichment of stable isotope leucine tracer. There will also be assessment of the activity of p70S6k and PHAS-1 (eLF4E-BP1), two key signaling proteins involved in translation initiation. In Specific Aim II, the effects of exercise and amino acid supplementation in vivo in subjects with a renal failure will be studied. The methods include infusion of L-1-13C leucine and a muscle biopsy before and after. The phosphorylation rate of PHAS-1 and p70S from biopsy tissue will be measured by gel electrophoresis and Western blot. A fractional synthetic rate will be calculated from measurements by mass spectrometry of protein and cytosolic enrichment of L-1-13C leucine. Groups will be treated either with saline infusion, exercise, or exercise and amino acid infusion. Subjects will be exercised for one hour on a cycle ergometer. There are many unanswered questions about how the body regulates the metabolism of protein in both healthy and disease states, such as renal failure. The goal of these studies is to provide a foundation leading to potential treatments targeted at particular mechanisms.